Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer.

BACKGROUND: Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil. METHODS: Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts. RESULTS: A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82%; arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively. CONCLUSION: Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial.

Chemoradiotherapy for cancer of the esophagus: contribution of the leucovorin, 5-fluorouracil bolus, and infusion-cisplatin-radiotherapy schedule starting with two neoadjuvant chemotherapy cycles: results from a pilot study.

To assess feasibility and tolerance of a modification in the usual radiochemotherapy regimen for esophageal cancer by using a leucovorin, 5-fluorouracil bolus, and infusion-cisplatin regimen (six cycles), beginning with two cycles of chemotherapy before conventional radiotherapy (50 Gy), 33 patients, 30 were men, 62.8 +/- 9.5 years, were treated for an esophageal carcinoma (29 squamous cell), 27 of these were in stage III (based on computed tomography scan). Neoadjuvant chemotherapy was well tolerated; concomitant radiochemotherapy was associated with severe adverse events mostly hematological in 23 patients. Complete response was achieved in 70%; median overall survival was 14 months, and 2-year survival was 40 +/- 11%. More than one-third of cycles could be performed as outpatients. This regimen seems safe and efficient, and could be conducted in an outpatient basis.

[French national evaluation for helicoidal tomotherapy: description of indications, dose constraints and set-up margins]. / Evaluation nationale de la tomothérapie hélicoïdale: description des indications, des contraintes de dose et des seuils de repositionnement.

After a request for proposal initiated by National Institute against cancer (INCa) in 2005, three French centers in France started tomotherapy in the first semester of 2007. A national policy of evaluation was performed to study the feasibility of this innovative technique and to compare the interest of helicoidal tomotherapy with other modalities of conformal therapy. Common protocols have been designed to facilitate this evaluation. Description of dose, IMRT levels and constraints are achieved according to each selected indication as: sarcoma, head and neck tumors, lung cancer, mesothelioma, bone metastases, anal carcinoma and craniospinal irradiation.

[Dose constraints to organs at risk for conformational and stereotactic radiotherapy: Small bowel and duodenum]. / Contraintes de doses aux organes à risque en radiothérapie conformationnelle et stéréotaxique : intestin grêle et duodénum.

Radiotherapy of abdominopelvic primary or secondary lesions in conformational or stereotactic techniques is in full development. The small bowel is highly sensitive to irradiation and is the main organ at risk limiting prescription doses. This literature review aims to define the dose constraints to the small bowel and the duodenum in conformational and stereotactic body radiotherapy. The small bowel including the duodenum, jejunum and ileum is delineated on the simulation scanner. The radio-induced intestinal toxicities are acute related to the cellular depopulation of the intestinal mucosa, and late of more complex pathophysiology associating depletion in stem cells, microangiopathy, chronic inflammation and fibrosis. The main predictive factor of intestinal toxicity is the dose-volume ratio. In conformational radiotherapy, the dose constraints to the duodenum are: V25Gy<45% and V35Gy<20%. The jejunum and ileum dose constraints are for delineation by intestinal loop or peritoneal cavity respectively: V15Gy<275mL or V15Gy<830mL and V45Gy<150mL. In stereotactic body radiotherapy, small bowel dose constraints depend on fractionation and are defined on a small volume and on a maximum dose at one point. Intestinal toxicity is also dependent on factors intrinsic to the patient and radiosensitizers such as targeted therapies or chemotherapies. With the development of new techniques allowing dose escalation on the tumour and the development of inverse planning, the definition of dose constraints to the small bowel is essential for current practice.

[Expected benefit of lymph node and seminal vesical dissection to decrease high-risk prostate cancer radiotherapy]. / Bénéfice attendu du curage ganglionnaire et de l'exérèse des vésicules séminales pour diminuer la toxicité de la radiothérapie des tumeurs prostatiques de haut risque.

PURPOSE: In case of pelvic lymph node and seminal vesicle dissection followed by prostate cancer intensity-modulated radiotherapy, the objective of the study was to evaluate the dosimetric benefit of reducing the target volume. PATIENTS AND METHODS: A total of 25 patients with high-risk prostate cancer had surgery first followed by intensity-modulated radiotherapy and androgen deprivation. Four treatment planning were simulated for each patient, based on two CT scans performed before and after surgery. The target volumes were: prostate-seminal vesicles-lymph nodes, prostate-lymph nodes, prostate-seminal vesicles and prostate only. The total dose was 46Gy in the seminal vesicles and lymph nodes, and 80Gy in the prostate. RESULTS: Compared to prostate target volume only, the addition of seminal vesicles and lymph nodes multiplied by a factor of 1.6 and 6.5 the target volume, respectively. Decreasing the target volume from prostate-seminal vesicles-lymph nodes to prostate-seminal vesicles, to prostate only decreased the rectal wall mean dose from 49Gy to 42Gy, to 36Gy, and the risk of late rectal bleeding from 4.4% to 3.2%, to 2.4% (P<0.05), respectively. The bladder wall mean dose decreased from 51Gy to 40Gy, to 35Gy (P<0,05), respectively. Not irradiating the lymph nodes decreased the absolute risk of diarrhea by 11%. CONCLUSION: Lymph node and seminal vesicle dissection before prostate cancer intensity-modulated radiotherapy allows decreasing moderately the risk of digestive toxicity.

[French organization of paediatric radiation treatment: Results of a survey conducted by the radiotherapy Committee of the French Society of Paediatric Cancers (SFCE)]. / Organisation française de la radiothérapie pédiatrique : résultats d'une enquête du comité radiothérapie de la Société française des cancers de l'enfant (SFCE).

PURPOSE: Radiotherapy is a rare indication in paediatric oncology, with 800 to 900 children in treatment per year in France. Child cancers represent approximately 1% of cancers in France and half occur before the age of 5 years. Paediatric radiation requires appropriate tools, local, time and specific training. In France, in 2015, 18 centres are accredited by the French National Cancer Institute (INCa) for this activity. MATERIAL AND METHODS: Survey conducted in February 2015 on the care of children (0 to 18 years) in radiotherapy departments in France. The survey was sent to the radiation oncologists involved in the 18 centres. The questions concerned the qualitative and quantitative aspect, medical and organizational aspects, and the involvement of assistant practitioners in the management of this activity. RESULTS: Seventeen centres responded. In 2014, 889 children under 18 were treated in radiotherapy departments. These departments are working together with one to four paediatric oncology departments. Regarding access to general anaesthesia: three centres perform one to seven treatment(s) under anaesthesia per year, three centres eight to ten treatments under anaesthesia per year, three centres ten to 24 treatments under anaesthesia per year and nine centres out of 17 use hypnosis techniques. In terms of human resources, in 2015, 29 radiation therapists have a paediatric radiotherapy activity. Involvement of assistant practitioners is growing and specific training are desired. Regarding treatment preparation and delivery, 13 centres have specific paediatric contentions, 14 of 16 centres employ radiation intensity modulated if dosimetry is more satisfying with 11 regularly to the craniospinal irradiation. Radiotherapy on moving areas with respiratory gating or hypofractionation is under developed. CONCLUSION: Paediatric radiation therapy is a specific activity requiring a dedicated management, both in human, organizational, medical and scientific aspects.

[French experience in paediatric total body irradiation: A study from the radiotherapy committee of the Société française des cancers de l'enfant (SFCE)]. / Expérience française de l'irradiation corporelle totale en pédiatrie : étude du comité de radiothérapie de la Société française des cancers de l'enfant (SFCE).

A survey was conducted in 2015 in France on the care of children in radiotherapy services. We present the results for total body irradiation in children, a specific technique of radiation treatment, which needs dedicated controls for this particular population. Of the 17 centres interviewed, 16 responded, and 13 practiced total body irradiation. Patients are positioned in lateral decubitus in 11 centres and supine/prone in two centres. Doses used for total body irradiation in myeloablative bone marrow transplantation are the same in all centres (12Gy); treatments are always fractionated. Lung shielding is positioned to limit the dose at an average of 8Gy with extremes ranging from 6 to 10Gy. The shape of the shieldings varies depending on departments' protocol, with a smaller size in case of mediastinal mass. Four centres have experience of total body irradiation under general anaesthesia, despite twice-daily fractions. In total, practice is relatively homogeneous throughout France and is inspired by the knowledge obtained in adults.

Neoadjuvant chemotherapy and hyperfractionated radiotherapy with concurrent low-dose chemotherapy for squamous cell esophageal carcinoma.

PURPOSE: We conducted a prospective study of neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction. METHODS AND MATERIALS: Thirty-two patients, 30 men, 2 women, mean age 56.2+/-8.9 years, with resectable squamous cell carcinoma of the esophagus (TNM stage I=4, IIA=4, IIB=13, III=11) were included. Chemotherapy, CDDP (80 mg/m2 D2), 5-fluorouracil (5-FU; 600 mg/m2, D1-4), and l-folinic acid (200 mg/m2, D1-4), was given in two sessions with a 3-week interval during which the patients received radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg injection of CDDP was given prior to each fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy. RESULTS: No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelets, mucositis) occurred in 16 patients and grade 4 effects (platelets, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n=18), persistent microscopic residues (n=4), or not significant modification (n=4). Survival at 1, 2, and 3 years was 81, 61, and 51.6% and disease-free survival was 75, 59, and 54% respectively. CONCLUSIONS: This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 3-year survival reached 52%, a very high rate in our experience.

Comparison of Cyfra 21-1, TPA and SCC tumor markers in esophageal squamous cell carcinoma.

The tumor markers Cyfra 21-1, TPA and SCC were assayed in a series of 96 patients with squamous cell carcinoma of the esophagus. Sensitivity was 42% for Cyfra 21-1, 40% for TPA and 37% for SCC. Combining Cyfra 21-1 and SCC gave a 56% sensitivity and combining TPA and SCC a 58% sensitivity. Sensitivity varied with disease stage and was particularly good in stage IV disease. Tumor markers did not vary with tumor differentiation. SCC levels were higher in tumors in the upper third of the esophagus. Pre-treatment levels of Cyfra 21-1 correlated with histological response. Cyfra 21-1 was also the only marker which distinguished significantly different survival curves. In multivariate analysis, however, treatment was the only independent factor predictive of survival.

Three cases of sarcoma occurring after radiation therapy of breast cancers.

We report 3 cases of sarcomas following irradiation for breast carcinoma. Median latent period ranged from 7 to 17 years. Histologic types were 1 malignant fibrous histiocytoma, 1 osteochondrosarcoma, 1 chondrosarcoma. Diagnosis was often delayed because of non-specific clinical features. The prognosis of these postirradiation sarcomas was poor with the median survival ranging from 10 to 70 months. One patient had a complete resection and is alive at 70 months. In the other 2 non-resectable patients, chemotherapy and/or radiotherapy did not induce an objective response. The poor prognosis when these tumors are diagnosed late emphasizes the need for increased awareness, which should lead to earlier diagnosis and, it is hoped, permit radical surgical treatment.

[Severe interstitial pneumopathy due to herpes virus after radiochemotherapy for esophageal carcinoma]. / Pneumopathies herpétiques sévères après radio-chimiothérapie de cancers de l'oesophage.

The authors report two cases of severe bilateral interstitial pneumopathies occurring after a medical treatment for esophageal carcinoma. In both cases a broncho-alveolar lavage revealed the presence of herpes virus and a specific treatment rapidly cured the patients.

[Cancer of the esophagus: outcome of neoadjuvant therapy on surgical morbidity and mortality]. / Cancer de l'oesophage: répercussion des thérapeutiques néoadjuvantes sur la morbidité et la mortalité opératoire.

Prognosis of oesophageal cancer is poor. There have been phase II-III trials of postoperative chemotherapy with the aim of improving survival. Chemoradiotherapy seems more promising than both chemotherapy and radiotherapy alone. In contrast, better results obtained with chemoradiotherapy were associated with an increase in morbidity and mortality, and finally overall survival was uncommonly improved. It is necessary to implement new multidisciplinary randomised trial.

[Target-volume and critical-organ delineation for conformal radiotherapy of prostate cancer: experience of French dose-escalation trials]. / Délimitation des volumes-cibles et des organes critiques pour la radiothérapie conformationnelle du cancer de la prostate: expérience des essais français d'escalade de dose.

The delineation of target volume and organs at risk depends on the organs definition, and on the modalities for the CT-scan acquisition. Inter-observer variability in the delineation may be large, especially when patient's anatomy is unusual. During the two french multicentric studies of conformal radiotherapy for localized prostate cancer, it was made an effort to harmonize the delineation of the target volumes and organs at risk. Two cases were proposed for delineation during two workshops. In the first case, the mean prostate volume was 46.5 mL (extreme: 31.7-61.3), the mean prostate and seminal vesicles volume was 74.7 mL (extreme: 59.6-80.3), the rectal and bladder walls varied respectively in proportion from 1 to 1.45 and from 1 to 1.16; in the second case, the mean prostate volume was 53.1 mL (extreme: 40.8-73.1), the volume of prostate plus seminal vesicles was 65.1 mL (extreme: 53.2-89), the rectal wall varied proportionally from 1 to 1, 24 and the vesical wall varied from 1 to 1.67. For participating centers to the french studies of dose escalation, a quality control of contours was performed to decrease the inter-observer variability. The ways to reduce the discrepancies of volumes delineation, between different observers, are discussed. A better quality of the CT images, use of urethral opacification, and consensual definition of clinical target volumes and organs at risk may contribute to that improvement.

[Preliminary results of the assessment of intensity modulated radiotherapy (IMRT) for prostatic and head and neck tumors (STIC 2001)]. / Résultats préliminaires de l'évaluation de la radiothérapie conformationnelle avec modulation d'intensité (RCMI) pour le traitement des cancers prostatiques et ORL (STIC 2001).

INTRODUCTION: Between May 2002 and May 2004, eight French comprehensive cancer centres did a prospective nonrandomized study including 200 patients, 100 with cancer of the prostate and 100 with head and neck cancers. Half of each patient group was treated by IMRT and the others by RTC 3D. This clinical study was associated with an economic study and a physics study. We report here the first results. PATIENTS AND METHODS: For the clinical study, the analysis of the data of the first 88 patients irradiated for a prostatic cancer shows that 39 received RTC and 49 IMRT with a mean dose of 78 Gy at the ICRU point at 2 Gy per fraction. For H&N tumours, the preliminary analysis was done on the 87 first patients with a mean follow-up of 11.5 months (2 to 25 months) and a median of 8.4 months for the IMRT groups and 13.2 months for the RTC group. The economic study was done on the first 157 patients included during the first 18 months: 71 treated by RTC (35 for H&N and 36 for prostate) and 86 treated by IMRT (38 for H&N and 48 for prostate). The assessment of the direct costs was realized by a micro-costing technique. The physical study compared dose distributions for both techniques and has created quality control recommendations. RESULTS: Clinical studies of the acute reactions do not show any difference between groups, but we want to point out the short follow-up and the relatively high dose delivered to cancers of the prostate. The physics study demonstrates that IMRT is technically feasible in good clinical conditions with high quality assurance, a good reproducibility and precision. Dosimetric data show that IMRT could certainly spare organs at risk more than RTC for H&N tumours. The direct costs of "routine" treatments for H&N tumours were 4922 euros for IMRT versus 1899 euros for RTC and for the prostatic cancers 4911 euros for IMRT versus 2357 for RTC.

[Breast adenomyoepithelioma. A case report and review of the literature]. / Adéno-myoépithéliome du sein. A propos d'un cas et revue de la littérature.

Adenomyoepithelioma of the breast is a rare tumor which exceptionally degenerates, requiring treatment and large exeresis. We report a new case and review the literature.

[Radiosurgical correlations of 61 breast microcalcification foci]. / Confrontation radiochirurgicale de 61 foyers de microcalcifications du sein.

OBJECTIVE. Diagnostic value of breast clustered microcalcifications discovered by mammography. DESIGN. A retrospective study. SETTING. Oncology Center of Rennes. SUBJECTS. 58 women (study group) with breast clustered microcalcifications without palpable tumour were operated. SURGERY. Prior to surgical removal of microcalcification, needle localization was performed. Histological results. We observed, 36 benign lesions (59%), 25 carcinomas (45%), 10 of them in situ and 15 infiltrative. RESULTS. Different radiological parameters were studied in relation to histological results, the vermicular morphology of microcalcification, an increased number, their triangular aspect, provide clue to the presence of breast carcinoma. The cluster of stippled calcification is not, in our series suggestive of a carcinoma, but also requires histopathological study, owig to the fact that in such cases, we have as many carcinomas as benign lesions. FINDING. Careful analysis of microcalcifications, within the clinical context, ensures a safe attitude, and enables one to operate only carcinomas.

[Breast cancer after treatment of Hodgkin's disease]. / Cancer du sein après traitement de maladie de Hodgkin.

OBJECTIVES: Development of diagnostic, therapeutic and preventive measures for breast cancer after cure of Hodgkin disease. STUDY TYPE: Presentation of 4 patients treated conjointly by the Radiotherapy and Gynaecology Surgery Departments of the Rennes University Hospital. RESULTS: Illustrations of difficult management of breast cancer at different stages of diagnosis and therapy. CONCLUSION: A past history of treated Hodgkin disease is a factor of risk for breast cancer and suggests the need for annual mammography screening 10 years after the end of treatment. Though more difficult, mastectomy is recommended over conservative radiosurgical treatment. The choice of drugs for adjuvant chemotherapy should rely on Hodgkin protocols and take into account heart function. Long-term carcinogenic effects of Hodgkin disease treatments requires modulation of the different treatment protocols as a function of stage, clinical and histological factors of prognosis and patient age.

[Immunoscintigraphy, an aid to the oncologist--the Rennes experience in using anti-CEA, anti-CA 19.9 monoclonal antibodies and radiolabelled OC-125]. / L'immunoscintigraphie, une aide pour le cancérologue--expérience rennaise de l'utilisation des anticorps monoclonaux anti-ACE, anti-CA 19.9 et OC-125 radiomarqués.

Immunoscintigraphy is steadily asserting itself as a valuable method in the localization of malignant tumours, alongside other imaging techniques. A monoclonal antibody specific to one or several tumour cell lines is used. The antibody is labelled with a gamma emitter radioisotope and so that it can be detected in vivo. We have evaluated three monoclonal antibodies (F(ab')2 fragments): a mixture of anti-CEA and anti-19.9 antibodies in the investigation of colorectal carcinoma and the antibody OC-125 in ovarian cancer. In our experience, it appears that pelvic recurrence is the best indication for immunoscintigraphy. Antibodies can apparently be safely used in man. We noted no side-effect following the injection of anti-CEA, anti 19.9 and OC-125.

[((18)F)-fluorodeoxyglucose PET/CT in cervix cancer: lymph node assessment and prognostic/predictive value of primary tumour analysis]. / Tomographie par émission de positons au ((18)F)-fluorodésoxyglucose dans les cancers du col utérin : évaluation ganglionnaire et valeur pronostique/prédictive des données de la tumeur primitive.

PURPOSE: In cervix carcinoma: (a) to evaluate the ability of ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the lymph node detection; (b) to investigate the prognostic and predictive value of the primary cervical PET parameters. PATIENTS AND METHODS: Ninety patients treated for cervix carcinoma and evaluated initially by MRI and FGD PET were included. The performances of FDG-PET for lymph node detection (relatively to the lymph node dissection) have been described (sensitivity, specificity, positive predictive value and negative predictive value). PET tumour parameters analyzed were: maximum standard uptake value (SUVmax), the volume and the maximum diameter. The prognostic and predictive values of these parameters were investigated. The tumour response was evaluated on surgical specimens. RESULTS: PET detected the cervical tumour with a sensitivity of 97% (mean values: SUVmax=15.8, volume=27 mm(3), maximum diameter=47). For the detection of the lymph nodes, the values of sensibility, specificity, positive predictive value and negative predictive value were: 86, 56, 69 and 78% in the pelvic, and 90, 67, 50 and 95% for the para-aortic area, respectively. The SUVmax was correlated with histologic response (P=0.04). The frequency of partial histological response was significantly higher for tumour SUVmax>10.9 (P=0.017). The maximum PET diameter and pathologic response had an impact on disease-free survival and overall survival in multivariate analysis (P<0.05). CONCLUSION: PET has high sensitivity in detecting pelvic and para-aortic lymph nodes. Some primary cervical tumour PET parameters are useful as prognostic and predictive factors.

[High dose for prostate irradiation with image guided radiotherapy: contribution of intensity modulation arctherapy]. / Haute dose dans la prostate par radiothérapie guidée par l'image: apport de l'arcthérapie avec modulation d'intensité du faisceau.

PURPOSE: To compare two Intensity Modulated Radiation Therapy (IMRT) techniques for prostate cancer: the Volumetric Modulated Arc Therapy (VMAT) and the "Step and Shoot" technique (S&S). MATERIALS AND METHODS: VMAT and S&S plans (RX 18MV) were created and compared (Wilcoxon test) for 10 patients. The dosimetric goal of both treatments was to deliver 46 Gy to the seminal vesicles and 80 Gy to the prostate, while respecting the dose constrains in the organs at risk of toxicity. For one patient, the two techniques were compared for dose painting and escalation in target volumes defined on MRI and registered thanks to intraprostatic fiducials. RESULTS: VMAT, compared to S&S, offered: an increase of the PTV2s (prostate) volume receiving 77 to 80 Gy and a decrease of V(82) and V(83); a decrease of V(4) to V(6), V(16) to V(23), and V(69) to V(73) for the rectal wall; a decrease of V(25) for the bladder wall; a decrease of V(21) to V(43) for the femoral heads; a decrease of V(26) to V(44) and V(72) to V(80) but an increase of V(1) to V(21) and V(49) to V(60) for the healthy tissues. The Conformal Index "COIN" was better with VMAT than S&S (0.60 to 0.66). The delivered MU were significantly reduced with VMAT (8% mean) as well as the delivery time (4 min to 1.5 min). VMAT allowed delivering theorically 90Gy in the peripheral zone and 100 Gy in the tumor. CONCLUSION: In case of prostate irradiation, VMAT shows improvement compared with S&S. In particular, organs at risk are better spared, the delivery time is shortened and the number of delivered UM is decreased.